C3、C4B1、ApoE在胰腺癌中的表达及临床意义
摘要
目的:探讨C3(补体3)、C4B1(补体4B1)、ApoE(载脂蛋白E)在胰腺癌中的表达及其与TNM分期和胰腺癌淋巴转移的相关性。
方法:将标本分为胰腺癌组和正常胰腺组,依据淋巴结转移情况将胰腺癌组分为有淋巴结转移组和无淋巴结转移组,依据TNM分期将胰腺癌组分为Ⅰ期组和Ⅱ-Ⅳ期组。分别应用免疫组织化学(二步法)、逆转录聚合酶链反应(Reverse Transcriptase Polymerase Chain Reaction,RT-PCR)和蛋白质印记(Western Blot)技术检测各组标本C3、C4B1、ApoE表达的差异性。
结果:C3、C4B1、ApoE在胰腺癌中均呈高表达;C3与肿瘤的TNM分期和有无淋巴结转移无相关性;C4B1、ApoE与肿瘤的TNM分期和有无淋巴结转移密切相关:Ⅱ-Ⅳ期胰腺癌和有淋巴转移的胰腺癌中的表达明显高于Ⅰ期胰腺癌和无淋巴转移的胰腺癌。
结论:C3、C4B1、ApoE在胰腺癌中均呈高表达;C3与肿瘤有无淋巴转移及TNM分期无关,说明C3只参与胰腺癌的早期事件,可能成为胰腺癌的早期诊断标记物;C4B1、ApoE与肿瘤发展密切相关,反映胰腺癌的生物学行为,可作为胰腺癌进展期预测指标。
Objectiv: To investigate the association of C3 , C4B1 and ApoE expressions with TNM stage and lymph node metastasis of human pancreatic cancer.
Methods:The specimens were divided into groups of pancreatic cancer group and normal pancreas, pancreatic cancer according to lymph node metastasis group was divided into lymph node metastasis and without lymph node metastasis, according to the TNM stage of pancreatic cancer group was divided into groupsⅠandⅡ-Ⅳof Group. Immunohistochemistry (two-step), Reverse Transcriptase Polymerase Chain Reaction,(RT-PCR) and Western Blot were detected by imprint technique C3, C4B1, ApoE expression differences.
Results: C3, C4B1, ApoE overexpressed in pancreatic cancer, C3 was not related with tumor’s lymph node metastasis and TNM stage, C4B1 and ApoE wer closely related with tumor’s lymph node metastasis and TNM stage: expression of C4B1 and ApoE in pancreatic cancer those with lymph node metastasis and stageⅡ-Ⅳwere significantly higher than those without lymph node metastasis and stageⅠ.
Conclusion: C3, C4B1, ApoE overexpressed in pancreatic cancer, C3 is not related with tumor’s lymph node metastasis and TNM stage, indicating that C3 is only an early event in pancreatic cancer, may be markers for early diagnosis of pancreatic cancer, C4B1, ApoE is closely related to tumor development, reflecting the biological behavior of pancreatic cancer and can be used as predictors of advanced pancreatic cancer.
方法:将标本分为胰腺癌组和正常胰腺组,依据淋巴结转移情况将胰腺癌组分为有淋巴结转移组和无淋巴结转移组,依据TNM分期将胰腺癌组分为Ⅰ期组和Ⅱ-Ⅳ期组。分别应用免疫组织化学(二步法)、逆转录聚合酶链反应(Reverse Transcriptase Polymerase Chain Reaction,RT-PCR)和蛋白质印记(Western Blot)技术检测各组标本C3、C4B1、ApoE表达的差异性。
结果:C3、C4B1、ApoE在胰腺癌中均呈高表达;C3与肿瘤的TNM分期和有无淋巴结转移无相关性;C4B1、ApoE与肿瘤的TNM分期和有无淋巴结转移密切相关:Ⅱ-Ⅳ期胰腺癌和有淋巴转移的胰腺癌中的表达明显高于Ⅰ期胰腺癌和无淋巴转移的胰腺癌。
结论:C3、C4B1、ApoE在胰腺癌中均呈高表达;C3与肿瘤有无淋巴转移及TNM分期无关,说明C3只参与胰腺癌的早期事件,可能成为胰腺癌的早期诊断标记物;C4B1、ApoE与肿瘤发展密切相关,反映胰腺癌的生物学行为,可作为胰腺癌进展期预测指标。
Objectiv: To investigate the association of C3 , C4B1 and ApoE expressions with TNM stage and lymph node metastasis of human pancreatic cancer.
Methods:The specimens were divided into groups of pancreatic cancer group and normal pancreas, pancreatic cancer according to lymph node metastasis group was divided into lymph node metastasis and without lymph node metastasis, according to the TNM stage of pancreatic cancer group was divided into groupsⅠandⅡ-Ⅳof Group. Immunohistochemistry (two-step), Reverse Transcriptase Polymerase Chain Reaction,(RT-PCR) and Western Blot were detected by imprint technique C3, C4B1, ApoE expression differences.
Results: C3, C4B1, ApoE overexpressed in pancreatic cancer, C3 was not related with tumor’s lymph node metastasis and TNM stage, C4B1 and ApoE wer closely related with tumor’s lymph node metastasis and TNM stage: expression of C4B1 and ApoE in pancreatic cancer those with lymph node metastasis and stageⅡ-Ⅳwere significantly higher than those without lymph node metastasis and stageⅠ.
Conclusion: C3, C4B1, ApoE overexpressed in pancreatic cancer, C3 is not related with tumor’s lymph node metastasis and TNM stage, indicating that C3 is only an early event in pancreatic cancer, may be markers for early diagnosis of pancreatic cancer, C4B1, ApoE is closely related to tumor development, reflecting the biological behavior of pancreatic cancer and can be used as predictors of advanced pancreatic cancer.
引文
1. Shaib YH, Davila JA, El-Serag HB. The epidemiology of pancreatic cancer in the United States: changes below the surface[J]. Aliment Pharmacol Ther, 2006, 24(1): 87-94.
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3. Rachagani S,Kumar S,Batra SK. MicroRNA in pancreatic cancer: Pathological, diagnostic and therapeutic implications[J].Cancer Letters, 2010,292(1):8-16.
4. Jiang L,Chen YC,Chan CY,et al.Down-regulation of stathmin is required for TGF-b inducible early gene 1 induced growth inhibition of pancreatic cancer cells [J]. Cancer Letters, 2009,274(1),101–108.
5. Satoh K, Hamada S, Kimura K,et al.Up-regulation of MSX2 enhances the Malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells[J].Am J pathol,2008,172(4):925-939.
6. Kikuchi S,Honda K,Tsuda H,et al.Expression and Gene Amplification of Actinin-4 in Invasive Ductal Carcinoma of the Pancreas[J]. Clin Cancer Res,2008,14(17): 5256-5348.
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8. Lowe D, Lee J, Schade R,et al. Patient with markedly elevated CA19-9 not associated with malignancy[J] .South Med J, 2006, 99(3): 306-308.
9. Kilic M, Gocmen E, Tez M,et al. Value of preoperative serum CA19-9 levels in predicting resectability for pancreatic cancer[J]. Can J Surg, 2006, 49(4) :241-244.
10. Marchese R, Muleti A, Pasqualetti P,et al. Low correspondence between K-ras mutations in pancreatic cancer tissue and detection of K-ras mutations in circulatingDNA[J]. Pancreas, 2006, 32(2): 171-177.
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17.汤厚阔,陈炯.肿瘤标记物CA19-9、CA242、CEA和CA125联合检测在胰腺癌诊断中的意义[J].肝胆胰外科杂志2009,21(2):95-97.
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23.刘晓川,孟垂华,刘铁夫,等.胰液K-ras密码子点突变联合血清CA19-9水平与胰腺癌复发关系的研究[J].临床消化病杂志, 2006,18(2):95-97.
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25.徐薇,翁玲,赵艳,等.胰液K-ras l2密码子点突变及血清CA1 9-9水平与胰腺癌复发关系[J].中国癌症杂志,2006,16(2):136-138.
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1. Shaib YH, Davila JA, El-Serag HB. The epidemiology of pancreatic cancer in the United States: changes below the surface[J]. Aliment Pharmacol Ther, 2006, 24(1): 87-94.
2. Guo X, Cui Z. Current diagnosis and treatment of pancreatic cancer in China[J]. Pancreas, 2005, 31(1): 13-22.
3. Wilkins M R ,Sanchez J C,Gooley a et al.Progress with proteome projects:Why all proteins expressed by genome should be identified and how to do it [J].Biotech Genet Eng Rev,1995,13(8):19.
4. Chang CY, Huang SP, Chin HM, et al. Low efficacy of serum levels of CA19-9 in prediction of malignant disease in asymptomatic population in Taiwan[J]. Hepatogastroenterology, 2006, 53(67): 1-4.
5. Lowe D, Lee J, Schade R, et al. Patient with markedly elevated CA19-9 not associated with malignancy[J] .South Med J, 2006, 99(3): 306-308.
6. Kilic M, Gocmen E, Tez M, et al. Value of preoperative serum CA19-9 levels in predicting resectability for pancreatic cancer[J]. Can J Surg, 2006, 49(4) :241-244.
7. Marchese R, Muleti A, Pasqualetti P,et al. Low correspondence between K-ras mutations in pancreatic cancer tissue and detection of K-ras mutations in circulating DNA[J]. Pancreas, 2006, 32(2): 171-177.
8. Campman SC, Fajardo MA, Rippon MB,et al. Adenosquamous carcinoma arising in a mucinous cystadenoma of the pancreas[J]. J Surg Oncol, 1997, 64(2): 159-162.
9. Wu X, Lu XH, Xu T,et al. Evaluation of the diagnostic value of serum tumor markers and fecal K-ras and p53 gene mutations for pancreatic cancer[J]. Chin J Dig dis, 2006, 7(3): 170-174.
10. Ohuchide K, Mizumoto K, Yamada D, et al. Quantitative analysis of humantelomerase reverse transcriptase in pancreatic cancer[J]. Clin Cancer Res, 2006, 12(7 Pt 1):2066-2069 .
11. Mishra G, Zhao Y, Sweeney J, et al. Determination of qualitative telomerase activity as an adjunct to the diagnosis of pancreatic adenocarcinoma by Es-guided fine needle aspiration[J] .Gastrointest Endosc, 2006, 63(4): 648-654.
12. Gold DV , Modrak DE , Ying Z , et al . New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis[J]. J Clin Oncol, 2006 , 24(2): 252-258.
13.马宁,葛春林,栾凤鸣,等。应用SELDI质谱技术筛选胰腺癌患者的血清标志蛋白[J].中国普通外科杂志, 2008, 17(3):242-245.
14. Gronborg M , Kristiansen TZ , Iwahori A , et al. Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach [J]. Mol Cell Proteomics. 2006 ,5(1): 157-171.
15. Chen R, Pan S, Yi EC, et al. Quantitative proteomic profiling of pancreatic cancer juice[J]. Proteomics, 2006, 6(13): 3871～3879.
16.朱峰,吕顺莉,高军,等.人胰腺癌胰液蛋白质差异表达分析[J].中国肿瘤临床, 2008,35(5):265-268.
17.田美,崔亚洲,宗美娟,等.胰腺癌胰液蛋白质组学分析[J].中华肿瘤防治杂志. 2008, 15(15): 1140-1143.
18.田锐,魏黎明,李延,等.人胰腺导管腺癌组织及癌旁组织双向电泳图谱的差异分析[J].中国普通外科杂志. 2007, 16(5): 433-437.
19. Deng R, Lu Z, Chen Y, et al. Plasma proteomic analysis ofpancreatic cancer by 2- dimensional gel electrophoresis [J]. Pancreas, 2007, 34(3): 310-317.
20. Zhao J, Simeone DM, Heidt D, et al. Comparative serum glycoproteomics using lectin selected sialic acid glycolproteins with mass spectrometric analysis: application to pancreatic cancer serum [J]. J Proteome Res, 2006, 5(7):1792-1802.
21. Honda K, Ono M, ShiTtashige M, et al. Early detection of pancreatic cancer by novel proteomic technique[J]. Nippon Rinsho, 2006, 64(9): 1745-1755.
22.刘晓川,孟垂华,刘铁夫,等.胰液K-ras密码子点突变联合血清CA19-9水平与胰腺癌复发关系的研究[J].临床消化病杂志, 2006, 18(2):95-97.
23.戴亚红,季秀英,张超,等.胰液K-ras基因突变和血清CA19-9联合检测判断胰腺癌复发[J].胰腺病学, 2005, 5(1):227-229.
24.徐薇,翁玲,赵艳,等.胰液K-ras l2密码子点突变及血清CA1 9-9水平与胰腺癌复发关系[J].中国癌症杂志, 2006, 16(2):136-138.
2. Guo X, Cui Z. Current diagnosis and treatment of pancreatic cancer in China[J]. Pancreas, 2005,31(1): 13-22.
3. Rachagani S,Kumar S,Batra SK. MicroRNA in pancreatic cancer: Pathological, diagnostic and therapeutic implications[J].Cancer Letters, 2010,292(1):8-16.
4. Jiang L,Chen YC,Chan CY,et al.Down-regulation of stathmin is required for TGF-b inducible early gene 1 induced growth inhibition of pancreatic cancer cells [J]. Cancer Letters, 2009,274(1),101–108.
5. Satoh K, Hamada S, Kimura K,et al.Up-regulation of MSX2 enhances the Malignant phenotype and is associated with twist 1 expression in human pancreatic cancer cells[J].Am J pathol,2008,172(4):925-939.
6. Kikuchi S,Honda K,Tsuda H,et al.Expression and Gene Amplification of Actinin-4 in Invasive Ductal Carcinoma of the Pancreas[J]. Clin Cancer Res,2008,14(17): 5256-5348.
7. Chang CY,Huang SP,Chin HM,et al. Low efficacy of serum levels of CA19-9 in prediction of malignant disease in asymptomatic population in Taiwan[J]. Hepatogastroenterology, 2006, 53(67): 1-4.
8. Lowe D, Lee J, Schade R,et al. Patient with markedly elevated CA19-9 not associated with malignancy[J] .South Med J, 2006, 99(3): 306-308.
9. Kilic M, Gocmen E, Tez M,et al. Value of preoperative serum CA19-9 levels in predicting resectability for pancreatic cancer[J]. Can J Surg, 2006, 49(4) :241-244.
10. Marchese R, Muleti A, Pasqualetti P,et al. Low correspondence between K-ras mutations in pancreatic cancer tissue and detection of K-ras mutations in circulatingDNA[J]. Pancreas, 2006, 32(2): 171-177.
11. Campman SC, Fajardo MA, Rippon MB, et al. Adenosquamous carcinoma arising in a mucinous cystadenoma of the pancreas[J]. J Surg Oncol, 1997,64(2): 159-162.
12. Wu X, Lu XH, Xu T, et al. Evaluation of the diagnostic value of serum tumor markers and fecal K-ras and p53 gene mutations for pancreatic cancer[J]. Chin J Dig dis, 2006, 7(3): 170-174.
13. Ohuchide K, Mizumoto K, Yamada D, et al. Quantitative analysis of human telomerase reverse transcriptase in pancreatic cancer[J]. Clin Cancer Res, 2006, 12(7):2066-2069 .
14. Mishra G, Zhao Y, Sweeney J,et al. Determination of qualitative telomerase activity as an adjunct to the diagnosis of pancreatic adenocarcinoma by Es-guided fine needle aspiration[J] .Gastrointest Endosc, 2006, 63(4): 648-654.
15. Koprowski H, Steplewski Z, Mitchell K , et al. Colorectal carcinoma antigens detected by hybridoma antibodies[J]. Somatic Cell Genet 1979; 5(6): 957-971.
16. Levy C, Lymp J, Angulo P, et al. The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis[J]. Dig Dis Sci 2005;50:1734-1740.
17.汤厚阔,陈炯.肿瘤标记物CA19-9、CA242、CEA和CA125联合检测在胰腺癌诊断中的意义[J].肝胆胰外科杂志2009,21(2):95-97.
18. Tian R, Wei LM, Qin WR, et al. Proteome Analysis of Human Pancreatic Ductal Adenocarcinoma Tissue Using Two-Dimensional Gel Electrophoresis and Tandem Mass Spectrometry for Identification of Disease-Related Proteins[J]. Dig Dis Sci, 2008,53:65–72.
19. Asmellash S, Mobley JA, Grizzle WE, et al. Applying Proteomic-Based Biomarker Tools for the Accurate Diagnosis of Pancreatic Cancer[J]. J Gastrointest Surg , 2008, 12(10):1683–1690.
20. Chen JH, Ni RZ, Xiao MB, et al. Comparative proteomic analysis of differentiallyexpressed proteins in human pancreatic cancer tissue[J]. Hepatobiliary Pancreat Dis, 2009, 8(2): 193-200.
21. Pan S, Chen R, Cooke K, et al. Quantitative proteomics investigation of pancreatic intraepithelial neoplasia[J]. Electrophoresis, 2009,30(7): 1132–1144.
22. Real FX. A“catastrophic hypothesis”forpancrea cancer progression[J]. Gastroenterology,2003,124(7):1958-1964.
23.刘晓川,孟垂华,刘铁夫,等.胰液K-ras密码子点突变联合血清CA19-9水平与胰腺癌复发关系的研究[J].临床消化病杂志, 2006,18(2):95-97.
24.戴亚红,季秀英,张超,等.胰液K-ras基因突变和血清CA19-9联合检测判断胰腺癌复发[J].胰腺病学, 2005, 5(1):227-229.
25.徐薇,翁玲,赵艳,等.胰液K-ras l2密码子点突变及血清CA1 9-9水平与胰腺癌复发关系[J].中国癌症杂志,2006,16(2):136-138.
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